The overall prevalence of heart valve disease in the United States, adjusted to the 2000 population, was estimated at that time to be 2.5%, with about 99,000 heart valve operations yearly. By 2011, it was estimated that roughly four million people in the United States were diagnosed annually with a heart valve disorder. Often, the only solution for degenerated or calcified heart valves is replacement of the entire valve, which up to now has been either a bioprosthetic or mechanical valve.
The first designs of replacement heart valves were for mechanical models, with major breakthroughs occurring in the 1950's and 1960's. The ball-in-cage design prevailed for many years until the tilting disc's emergence. The pyrolytic carbon bileaflet valve was designed in the 1970's and became the ‘gold standard’ for mechanical valve replacement. Since St. Jude Medical introduced the pyrolytic carbon valve much of the innovation in this area has come to a halt and only minor features of mechanical valves have evolved over the last forty years.
Although mechanical valves are the most durable solution for heart valve replacements (typically said to last for 20-30 years) thrombogenicity of the artificial surfaces remains a cause for much concern. Not only are the devices non-biological, they also introduce turbulent flow regimes. The turbulence can activate platelets which in turn initiate the formation of thrombi. To prevent this from occurring, patients are put on life-long anticoagulant therapy that involves the administration of Warfarin. Unfortunately, because Warfarin decreases the blood's ability to coagulate on the valve it also prevents coagulation systemically, leaving the patient vulnerable to major bleeding events. The reliance upon an expensive drug therapy and the necessity of close patient monitoring is undesirable and the main factor that has kept mechanical valve replacement out of developing countries.
A solution to the increased thrombogenicity of mechanical valves was the advent of bioprosthetic valve (BPV) technology. These valves are made from either porcine aortic valves or bovine pericardium that has been chemically fixed, cross-linking the tissue and masking the antigens present in the xenogeneic materials. BPVs are predicted to last 10-15 years, which is a lower expectation than that of mechanical valves. In addition, it has been found that after 15 years all-cause mortality is lower for patients implanted with mechanical valves as compared to BPVs. Although the mechanical valve has been shown to be more durable and can be projected to last longer, the BPV is still the best choice for those patients who cannot be put on anticoagulant regimes. In addition, certain patient populations preferably receive certain valves. For example elderly patients (65 years and older) typically receive BPVs because of expected life span and the reduced chance for calcification, and younger patients/children receive mechanical valves due to the decreased number of expected replacements required.
More recently, tissue engineering approaches have been developed that seek to make curative solutions for patients who are seeking long-term treatment of disease and tissue degeneration. The constructs that are being researched and tested will not simply compensate for the damaged tissue; the aim is to create living tissue that can be implanted into a human that will, from that point on, grow and remodel. Ideally, a tissue engineered heart valve will resemble both the size and shape of the native valve; be durable and fully functioning with good hemodynamics; be non-immunogenic, non-inflammatory, non-thrombogenic, and non-obstructive; respond to mechanical and biological cues appropriately; grow in size with the recipient; and will adapt to changing conditions throughout the life of the recipient and valve.
Whether for study or implantation, natural and synthetic heart valve tissue (e.g., BHV and engineered tissue) is generally subjected to multiple treatment regimes. For instance, xenograft valve tissue must be decellularized to remove the native cells prior to either testing or implant. In addition, mechanical testing by use of a conditioning system can be carried out to examine and alter tissue strength or to ensure suitable strength prior to implant, Seeding of natural or synthetic scaffolds can also be carried out in development of new valves and/or to encourage integration with a recipient's natural tissue following implantation.
It has been common to secure valve tissue during the various treatment regimens by temporarily suturing or clipping the tissue to mounting rings. Unfortunately, physically attaching the tissue to the holding device can damage the tissue and cause mechanical weakening of the tissue. Moreover, securement systems generally do not provide a method for securing the tissue with a tight seal, and fluid leakage around the tissue during the treatment protocols can prevent effective conditioning and/or testing. Additionally, the tissue characteristics can change during treatment. For instance decellularization can lead to a loss of tissue volume, and presently known systems do not account for the physical changes of the tissue associated with a volume loss. Thus, with present systems, the tissue can become loose in/on the holder and/or leaks can form between the tissue and the holder as decellularization takes place.
What is needed in the art is a tissue holder that can effectively grip tissue during conditioning and/or testing. For instance, a heart valve tissue holder that can provide for totally hands-free and secure retention during multiple treatment regimens would be of great benefit for natural or synthetic heart valve tissue for research and development protocols as well as for implantation protocols.